The EGF receptor (EGFR) is overexpressed in many human tumors implicating it in the pathogenesis of some cancers. To study regulation of the EGFR gene, the promoter region was isolated and shown to contain many transcription factor binding sites. The expression of the EGF receptor (EGFR) gene is governed by the interaction with the GC-rich promoter region of the gene of transcription factors that activate (Spl and ETF) or repress (GCF) transcription. To examine the relationship between EGFR expression and GCF expression, we have analyzed the level of GCF RNA in human tissues and cancer cell lines. We have also examined the level of GCF RNA after treatment of cells with agents that regulate EGFR expression. Three RNA species hybridize to the GCF cDNA and fragments of the cDNA have been used to determine the relationship of these RNA species. The chromosomal localization of the GCF gene has been determined by in situ hybridization. The GCF cDNA has been placed under control of the metal inducible metallothionein promoter and three lines of transgenic mice have been generated that express GCF mRNA.